E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Cancers arising from the ovary, fallopian tube, or abdomen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase 1b - to determine the recommended Phase 2 dose of LY2228820 that can be safely administered with gemcitabine and carboplatin
Phase 2 - to compare the progression-free survival in patients treated with LY2228820 plus gemcitabine and carboplatin versus placebo plus gemcitabine and carboplatin |
|
E.2.2 | Secondary objectives of the trial |
1. Change in tumor size, CA 125, overall response rate, overall survival
2. Safety and tolerability of the combination of LY2228820 with gemcitabine and carboplatin
3. Pharmacokinetics (PK) of LY2228820 and evaluation for effect of LY2228820 on the PK of gemcitabine, its metabolite (dFdU), and carboplatin
4. Biomarkers related to the p38 MAPK pathway activity and the pathogenesis of ovarian cancer
5. Patient-reported outcomes |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women ≥ 18 years of age
Have cytologic or histologic proven epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
Have recurrence of cancer at least 6 months after completion of first-line platinum based therapy
Phase 1b - have either measureable or non-measureable disease. Phase 2 - have at least 1 measureable lesion assessable using Response Evaluation Criteria in Solid Tumors
Have ECOG performance status ≤ 2
Have discontinued all previous therapies for cancer at least 14 days prior to starting study. Previous radiotherapy must be discontinued at least 21 days prior to start of study
Have adequate organ function: Hematology: absolute neutrophil count ≥ 1.5 x 10x9/L, platelets ≥ 100 x 10x9/L, hemoglobin ≥ 8g/dL. Hepatic: billirubin ≤ 1.5 times upper limits of normal, alanin aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limits of normal. Renal: calculated creatinine clearance ≥ 50ml/min
If applicable, have a negative pregnancy test and agree to a reliable method of birth control while receiving investigational product and for 3 months following the last dose of study drug
Are able to swallow tablets
Have given written informed consent/assent prior to any study specific procedures |
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E.4 | Principal exclusion criteria |
Are currently enrolled in another clinical trial involved in investigational drug or device
Have previously taken LY2228820Have previously been treated with gemcitabine for ovarian, fallopian tube, or primary peritoneal cancer
Receiving any cytotoxic or other cancer treatment
Have had a major bowel resection that the physician determines would alter oral drug absorption
Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis)
Require concurrent administration of immunosupressive therapy
Intermittent corticosteroids used as part of an antiemetic regimen are permitted.
Have known central nervous system malignancy or metastasis
Have a concurrent or previous malignancy, unless that prior malignancy was treated with definitive therapy at least 5 years previously with no evidence of recurrence.
Have serious concomitant systemic disorders incompatible with the study
Have received more than one previous chemotherapy regimen for ovarian cancer
Have any diagnosis of ovarian borderline tumor
Are pregnant or lactating women
Are receiving concurrent therapy that the physician determines is immunosuppressive
Have known central nervous system malignancy or metastasis
Have a concurrent or previous malignancy, unless that prior malignancy was treated with definitive therapy at least 5 years previously with no evidence of recurrence.
Have a serious systemic disorder that the physician determines is incompatible with the study
Have received more than one previous chemotherapy regimen for ovarian cancer
Have tumor of borderline malignancy
Are pregnant or lactating women |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1b – Safety and dose
Phase 2 – Progression free survival. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase 1b - after all evaluable patients have received at least 1 cycle of study treatment
Phase 2 - after 79 PFS events have occurred |
|
E.5.2 | Secondary end point(s) |
Change in tumor size, CA125, overall response rate, overall survival
Safety and tolerability of the combination of LY2228820, gemcitabine, and carboplatin
Pharmacokinetics of LY2228820, gemcitabine and its metabolite (dFdU), and carboplatin
Biomarkers related to p38 MAPK pathway activity and the pathogenesis of ovarian cancer
Patient-reported outcomes |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase 1b: N/A
Phase II: After 30 patients in have received 1 cycle of study
therapy, after 60 patients have received at least 2 cycles of
therapy, and final analysis is 2 years after completion of
enrollment. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Germany |
India |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |